medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-18-106-117medsovet-6559Research ArticleПРАКТИКАPRACTICEЭффективность азоксимера бромида в терапии госпитализированных пациентов с внебольничной пневмонией среднетяжелого и тяжелого теченияEfficacy of azoximer bromide in the treatment of hospitalized patients with moderate to severe community-acquired pneumoniahttps://orcid.org/0000-0002-6348-6867ЗыряновС. К.ZyryanovS. K.

Зырянов Сергей Кенсаринович – доктор медицинских наук, профессор, заведующий кафедрой общей и клинической фармакологии, РУДН; заместитель главного врача, ГКБ №24.

117198, Москва, ул. Миклухо-Маклая, д. 6; 127015, Москва, ул. Писцовая, д. 10.

Sergey K. Zyryanov - Dr. Sci. (Med.), Professor, Head of Department of General and Clinical Pharmacology, Peoples' Friendship University of Russia; Deputy Chief Medical Officer, City Clinical Hospital No. 24.

6, Miklukho-Maklay St., Moscow, 117198; 10, Piscovaya St., Moscow, 127015.

zyryanov_sk@rudn.universityhttps://orcid.org/0000-0001-7729-2169БутрановаО. И.ButranovaO. I.

Бутранова Ольга Игоревна – кандидат медицинских наук, доцент кафедры общей и клинической фармакологии Медицинского института.

117198, Москва, ул. Миклухо-Маклая, д. 6.

Olga I. Butranova - Cand. Sci. (Med.), Associate Professor of Department of General and Clinical Pharmacology, Institute of Medicine, Peoples' Friendship University of Russia.

6, Miklukho-Maklay St., Moscow, 117198.

butranova-oi@rudn.ruhttps://orcid.org/0000-0002-3003-4362ЕршовА. В.ErshovA. V.

Ершов Антон Валерьевич – доктор медицинских наук, ведущий научный сотрудник научно-исследовательского института общей реаниматологии, ФНКЦ РР; профессор кафедры патофизиологии, ПМГМУ им. И.М. Сеченова.

107031, Москва, ул. Петровка, д. 25, корп. 2; 127994, Москва, Рахмановский пер, д. 3.

Anton V. Ershov - Dr. Sci. (Med.), Lead Research Associate, Research Institute of General Reanimatology, Federal Scientific and Clinical Center for Reanimatology and Rehabilitation; Professor of Department of Pathophysiology, Sechenov First Moscow State Medical University (Sechenov University).

25, Bldg. 2, Petrovka St., Moscow, 107031; 8, Bldg. 2, Rakhmanovskiy lane, Moscow, 119991.

salavatprof@mail.ruhttps://orcid.org/0000-0002-3003-4362МанасоваЗ. Ш.ManasovaZ. Sh.

Манасова Зарипат Шахбановна - кандидат медицинских наук, доцент кафедры патофизиологии.

127994, Москва, Рахмановский пер, д. 3.

Zaripat Sh. Manasova - Cand. Sci. (Med.), Associate Professor of Department of Pathophysiology, Sechenov First Moscow State Medical University (Sechenov University).

8, Bldg. 2, Rakhmanovskiy lane, Moscow, 119991.

zmanasova@yandex.ruРоссийский университет дружбы народов; Городская клиническая больница №24РоссияPeoples' Friendship University of Russia; City Clinical Hospital No.24Russian FederationРоссийский университет дружбы народовРоссияPeoples' Friendship University of RussiaRussian FederationПервый Московский государственный Медицинский университет имени И.М. Сеченова (Сеченовский университет); Федеральный научно-клинический центр реаниматологии и реабилитологииРоссияSechenov First Moscow State Medical University (Sechenov University); Federal Scientific and Clinical Center for Reanimatology and RehabilitationRussian FederationПервый Московский государственный Медицинский университет имени И.М. Сеченова (Сеченовский университет)РоссияSechenov First Moscow State Medical University (Sechenov University)Russian Federation202101122021018106117Copyright © Зырянов С.К., Бутранова О.И., Ершов А.В., Манасова З.Ш., 20212021Зырянов С.К., Бутранова О.И., Ершов А.В., Манасова З.Ш.Zyryanov S.K., Butranova O.I., Ershov A.V., Manasova Z.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/6559Введение

Введение. Широкое распространение внебольничной пневмонии и высокий уровень осложнений в случае ее тяжелого течения делают актуальным поиск новых фармакотерапевтических инструментов, способных повысить эффективность стандартных схем ведения пациентов. Высокий уровень выраженности воспалительных реакций лежит в основе высокого риска септических осложнений пневмонии наравне с нарушениями в иммунном ответе.

Цель - оценить эффективность включения азоксимера бромида в комплексную схему терапии госпитализированных пациентов с внебольничной пневмонией среднетяжелого и тяжелого течения.

Материалы и методы

Материалы и методы. Открытое рандомизированное проспективное исследование в параллельных группах для сравнения эффективности включения азоксимера бромида в комплексную терапию госпитализированных пациентов с внебольничной пневмонией среднетяжелого и тяжелого течения было проведено на базе Федерального научно-клинического центра реаниматологии и реабилитологи». Исследуемая группа - 30 пациентов, группа сравнения - 37. Исходные характеристики были сопоставимы в обеих группах.

Результаты

Результаты. Включение азоксимера бромида в комплексное лечение пациентов с внебольничной пневмонией способствовало достоверному снижению длительности госпитализации (Ме (LQ; HQ): 9 (8; 10) дней для исследуемой группы и 13 (10; 14) дней для группы сравнения, (р = 0,000078), длительности пребывания в ОРИТ (Ме (LQ; HQ): 2 суток (1,5; 2,5) и 5 суток (5,0; 6,0) соответственно (р = 0,00001), длительности фебрильной лихорадки 5 (±0,6) суток против 10 (±1,2) суток (р = 0,0000), частоты развития острой дыхательной недостаточности (13,33% в 1-й группе против 37,84% во 2-й группе, р = 0,024) и септического шока (10% в 1-й группе против 32,43% во 2-й группе, р = 0,0285).

Выводы

Выводы. Включение азоксимера бромида в стандартную схему терапии пациентов с внебольничной пневмонией позволило сократить длительность госпитализации, длительность пребывания в ОРИТ, длительность фебрильной лихорадки, частоту развития септического шока и дыхательной недостаточности. Возможные механизмы могут включать снижение выраженности воспалительных реакций и оптимизацию иммунного ответа организма пациента на инфекционный процесс.

Introduction

Introduction. The high incidence of community-acquired pneumonia and the high complication rates in the cases of severe pneumonia actualize the search for new pharmacotherapy tools to improve the effectiveness of standard patient management regimens. A high level of severe inflammatory response underlies the high risk for developing septic complications of pneumonia, along with impaired immune responses.

The aim is to evaluate the efficacy of azoximer bromide introduction in the combination therapy regimen for hospitalized patients with moderate to severe community-acquired pneumonia.

Materials and methods

Materials and methods. A prospective, open label, parallel group, randomized study comparing the efficacy of azoximer bromide introduction in the combination therapy of hospitalized patients with moderate to severe community-acquired pneumonia was conducted at the premises of Federal Scientific and Clinical Center for Reanimatology and Rehabilitation. 30 patients were included in the study group and 37 patients in the comparator group. The baseline characteristics were comparable in both groups. Results. The azoximer bromide introduction in the combination therapy of patients with community-acquired pneumonia led to a statistically significant reduction in the duration of hospital stay (Me (LQ; HQ): 9 (8; 10) days for the study group and 13 (10; 14) days for the comparator group, (p = 0.000078), duration of ICU stay (Me (LQ; HQ) 2 days (1.5; 2.5) and 5 days (5.0; 6.0), respectively, (p = 0.00001), the duration of febrile fever 5 (± 0.6) days versus 10 (± 1.2) days (p = 0.0000), the incidence of acute respiratory failure (13.33% in group 1 versus 37.84% in group 2, p = 0.024) and septic shock (10% in group 1 versus 32.43% in group 2, p = 0.0285).

Conclusions

Conclusions. The azoximer bromide introduction in the standard therapy regimen for patients with community-acquired pneumonia allowed to reduce the duration of hospital stay, the duration of ICU stay, the length of febrile fever, the incidence of septic shock and respiratory failure. The possible mechanisms of action may include a reduction of the severe inflammatory reactions and an optimization of the patient's immune response to the infectious process.

внебольничная пневмонияазоксимера бромиддлительность госпитализациисептические осложненияcommunity-acquired pneumoniaazoximer bromideduration of hospital stayseptic complicationsReferencesTorres A., Peetermans W.E., Viegi G., Blasi F. Risk factors for community-acquired pneumonia in adults in Europe: a literature review. Thorax. 2013;68(11):1057-1065. https://doi.org/10.1136/thoraxjnl-2013-204282.Torres A., Peetermans W.E., Viegi G., Blasi F. Risk factors for community-acquired pneumonia in adults in Europe: a literature review. Thorax. 2013;68(11):1057-1065. https://doi.org/10.1136/thoraxjnl-2013-204282.Theilacker C., Sprenger R., Leverkus F., Walker J., Hackl D., von Eiff C., Schiffner-Rohe J. Population-based incidence and mortality of community-acquired pneumonia in Germany. PLoS ONE. 2021;16(6):e0253118. https://doi.org/10.1371/journal.pone.0253118.Theilacker C., Sprenger R., Leverkus F., Walker J., Hackl D., von Eiff C., Schiffner-Rohe J. Population-based incidence and mortality of community-acquired pneumonia in Germany. PLoS ONE. 2021;16(6):e0253118. https://doi.org/10.1371/journal.pone.0253118.Partouche H., Lepoutre A., Vaure C.B.D., Poisson T., Toubiana L., Gilberg S. Incidence of all-cause adult community-acquired pneumonia in primary care settings in France. Med Mal Infect. 2018;48(6):389-395. https://doi.org/10.1016/j.medmal.2018.02.012.Partouche H., Lepoutre A., Vaure C.B.D., Poisson T., Toubiana L., Gilberg S. Incidence of all-cause adult community-acquired pneumonia in primary care settings in France. Med Mal Infect. 2018;48(6):389-395. https://doi.org/10.1016/j.medmal.2018.02.012.Lopardo G.D., Fridman D., Raimondo E., Albornoz H., Lopardo A., Bagnulo H. et al. Incidence rate of community-acquired pneumonia in adults: a population-based prospective active surveillance study in three cities in South America. BMJ Open. 2018;8(4):e019439. Available at: https://pub-med.ncbi.nlm.nih.gov/29643153/.Lopardo G.D., Fridman D., Raimondo E., Albornoz H., Lopardo A., Bagnulo H. et al. Incidence rate of community-acquired pneumonia in adults: a population-based prospective active surveillance study in three cities in South America. BMJ Open. 2018;8(4):e019439. Available at: https://pub-med.ncbi.nlm.nih.gov/29643153/.McLaughlin J.M., Khan F.L., Thoburn E.A., Isturiz R.E., Swerdlow D.L. Rates of hospitalization for community-acquired pneumonia among US adults: A systematic review. Vaccine. 2020;38(4):741-751. https://doi.org/10.1016/j.vaccine.2019.10.101.McLaughlin J.M., Khan F.L., Thoburn E.A., Isturiz R.E., Swerdlow D.L. Rates of hospitalization for community-acquired pneumonia among US adults: A systematic review. Vaccine. 2020;38(4):741-751. https://doi.org/10.1016/j.vaccine.2019.10.101.Metlay J.P., Waterer G.W., Long A.C., Anzueto A., Brozek J., Crothers K. et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45-e67. https://doi.org/10.1164/rccm.201908-1581ST.Metlay J.P., Waterer G.W., Long A.C., Anzueto A., Brozek J., Crothers K. et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45-e67. https://doi.org/10.1164/rccm.201908-1581ST.Tansarli G.S., Mylonakis E. Systematic Review and Meta-analysis of the Efficacy of Short-Course Antibiotic Treatments for Community-Acquired Pneumonia in Adults. Antimicrob Agents Chemother. 2018;62(9):e00635-e00718. https://doi.org/10.1128/AAC.00635-18.Tansarli G.S., Mylonakis E. Systematic Review and Meta-analysis of the Efficacy of Short-Course Antibiotic Treatments for Community-Acquired Pneumonia in Adults. Antimicrob Agents Chemother. 2018;62(9):e00635-e00718. https://doi.org/10.1128/AAC.00635-18.Marshall D.C., Goodson R.J., Xu Y., Komorowski M., Shalhoub J., Maruthappu M., Salciccioli J.D. Trends in mortality from pneumonia in the Europe union: a temporal analysis of the European detailed mortality database between 2001 and 2014. Respir Res. 2018;19(1):81. https://doi.org/10.1186/s12931-018-0781-4.Marshall D.C., Goodson R.J., Xu Y., Komorowski M., Shalhoub J., Maruthappu M., Salciccioli J.D. Trends in mortality from pneumonia in the Europe union: a temporal analysis of the European detailed mortality database between 2001 and 2014. Respir Res. 2018;19(1):81. https://doi.org/10.1186/s12931-018-0781-4.Rendon A., Rendon-Ramirez E.J., Rosas-Taraco A.G. Relevant Cytokines in the Management of Community-Acquired Pneumonia. Curr Infect Dis Rep. 2016;18(3):10. https://doi.org/10.1007/s11908-016-0516-y.Rendon A., Rendon-Ramirez E.J., Rosas-Taraco A.G. Relevant Cytokines in the Management of Community-Acquired Pneumonia. Curr Infect Dis Rep. 2016;18(3):10. https://doi.org/10.1007/s11908-016-0516-y.International Union of Immunological Societies Expert Committee on Primary Immunodeficiencies, Notarangelo L.D., Fischer A., Geha R.S., Casanova J..L, Chapel H., Conley M.E. et al. Primary immunodeficiencies: 2009 update. J Allergy Clin Immunol. 2009;124(6):1161-1178. https://doi.org/10.1016/j.jaci.2009.10.013.International Union of Immunological Societies Expert Committee on Primary Immunodeficiencies, Notarangelo L.D., Fischer A., Geha R.S., Casanova J..L, Chapel H., Conley M.E. et al. Primary immunodeficiencies: 2009 update. J Allergy Clin Immunol. 2009;124(6):1161-1178. https://doi.org/10.1016/j.jaci.2009.10.013.de la Torre M.C., BoUbar I., Vendrell M., de Gracia J., Vendrell E., Rodrigo M.J. et al. Serum immunoglobulins in the infected and convalescent phases in community-acquired pneumonia. Respir Med. 2013;107(12):2038-2045. https://doi.org/10.1016/j.rmed.2013.09.005.de la Torre M.C., BoUbar I., Vendrell M., de Gracia J., Vendrell E., Rodrigo M.J. et al. Serum immunoglobulins in the infected and convalescent phases in community-acquired pneumonia.Respir Med. 2013;107(12):2038-2045. https://doi.org/10.1016/j.rmed.2013.09.005.Trabattoni D., Clerici M., Centanni S., Mantero M., Garziano M., Blasi F. Immunomodulatory effects of pidotimod in adults with community-acquired pneumonia undergoing standard antibiotic therapy. Pulm Pharmacol Ther. 2017;44:24-29. https://doi.org/10.1016/j.pupt.2017.03.005.Trabattoni D., Clerici M., Centanni S., Mantero M., Garziano M., Blasi F. Immunomodulatory effects of pidotimod in adults with community-acquired pneumonia undergoing standard antibiotic therapy. Pulm Pharmacol Ther. 2017;44:24-29. https://doi.org/10.1016/j.pupt.2017.03.005.Welte T., Dellinger R.P., Ebelt H., Ferrer M., Opal S.M., Singer M. et al. Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study). Intensive Care Med. 2018;44(4):438-448. https://doi.org/10.1007/s00134-018-5143-7.Welte T., Dellinger R.P., Ebelt H., Ferrer M., Opal S.M., Singer M. et al. Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study). Intensive Care Med. 2018;44(4):438-448. https://doi.org/10.1007/s00134-018-5143-7.Петров Р.В., Хаитов Р.М., Некрасов А.В., Атаулаханов Р.И., Пинегин Б.В., Пучкова А.С. и др. Полиоксидоний - иммуномодулятор последнего поколения: итоги трехлетнего клинического применения. Аллергия, астма и клиническая иммунология. 1999;(3):3-6.Petrov R.V., Khaitov R.M., Nekrasov A.V., Ataullakhanov R.I., Pinegin B.V., Puchkova A.S. et al. Polyoxidonium, a New-Generation Immunomodulator: Experience From a Three Years Clinical Application. Allergiya, astma i klinicheskaya immunologiya = Allergies, Asthma and Clinical Immunology. 1999;(3):3-6. (In Russ.)Dyakonova V.A., Dambaeva S.V., Pinegin B.V., Khaitov R.M. Study of interaction between the polyoxidonium immunomodulator and the human immune system cells. Int Immunopharmacol. 2004;4(13):1615-1623. https://doi.org/10.1016/j.intimp.2004.07.015.Dyakonova V.A., Dambaeva S.V., Pinegin B.V., Khaitov R.M. Study of interaction between the polyoxidonium immunomodulator and the human immune system cells. Int Immunopharmacol. 2004;4(13):1615-1623. https://doi.org/10.1016/j.intimp.2004.07.015.Toptygina A., Semikina E., Alioshkin V. Influence of an immunopotentiator Polyoxidonium on cytokine profile and antibody production in children vaccinated with Priorix. Arch Physiol Biochem. 2012;118(4):197-203. https://doi.org/10.3109/13813455.2012.659669.Toptygina A., Semikina E., Alioshkin V. Influence of an immunopotentiator Polyoxidonium on cytokine profile and antibody production in children vaccinated with Priorix. Arch Physiol Biochem. 2012;118(4):197-203. https://doi.org/10.3109/13813455.2012.659669.Alexia C., Cren M., Louis-Plence P., Vo D.N., El Ahmadi Y., Dufourcq-Lopez E. et al. Polyoxidonium® Activates Cytotoxic Lymphocyte Responses Through Dendritic Cell Maturation: Clinical Effects in Breast Cancer. Front Immunol. 2019;10:2693. https://doi.org/10.3389/fimmu.2019.02693.Alexia C., Cren M., Louis-Plence P., Vo D.N., El Ahmadi Y., Dufourcq-Lopez E. et al. Polyoxidonium® Activates Cytotoxic Lymphocyte Responses Through Dendritic Cell Maturation: Clinical Effects in Breast Cancer. Front Immunol. 2019;10:2693. https://doi.org/10.3389/fimmu.2019.02693.Grivtsova L.Y., Falaleeva N.A., Tupitsyn N.N. Azoximer Bromide: Mystery, Serendipity, and Promise. Front Oncol. 2021;11:699546. https://doi.org/10.3389/fonc.2021.699546.Grivtsova L.Y., Falaleeva N.A., Tupitsyn N.N. Azoximer Bromide: Mystery, Serendipity, and Promise. Front Oncol. 2021;11:699546. https://doi.org/10.3389/fonc.2021.699546.Efimov S.V., Matsiyeuskaya N.V., Boytsova O.V., Akhieva L.Y., Kvasova E.I., Harrison F. et al. The effect of azoximer bromide (Polyoxidonium®) in patients hospitalized with coronavirus disease (COVID-19): an open-label, multicentre, interventional clinical study. Drugs Context. 2021;10:2020-11-1. https://doi.org/10.7573/dic.2020-11-1.Efimov S.V., Matsiyeuskaya N.V., Boytsova O.V., Akhieva L.Y., Kvasova E.I., Harrison F. et al. The effect of azoximer bromide (Polyoxidonium®) in patients hospitalized with coronavirus disease (COVID-19): an open-label, multicentre, interventional clinical study. Drugs Context. 2021;10:2020-11-1. https://doi.org/10.7573/dic.2020-11-1.Синопальников А.И. Американские (atS/idSa, 2019) и российские (РРо/ МакМах, 2019) рекомендации по ведению внебольничной пневмонии у взрослых. Два взгляда на актуальную проблему. Consilium Medicum. 2020;22(3):22-27. https://doi.org/10.26442/20751753.2020.3.200084.Sinopalnikov A.I. United States (ATS/IDSA, 2019) and Russian (RRS/IACMAC, 2019) guidelines on community-acquired pneumonia management in adults. Two points of view on a pressing issue. Consilium Medicum. 2020;22(3):22-27. (In Russ.) https://doi.org/10.26442/20751753.2020.3.200084.Чучалин А.Г., Синопальников А.И., Козлов Р.С., Авдеев С.Н., Тюрин И.Е., Руднов В.А. Внебольничная пневмония: клинические рекомендации. 2018. М.; 2018. 98 с. Режим доступа: https://spulmo.ru/obrazovatelnye-resursy/federalnye-klinicheskie-rekomendatsii/.Chuchalin A.G., Sinopalnikov A.I., Kozlov R.S., Avdeev S.N., Tyurin I.E., Rudnov V.A. Community- acquired pneumonia: clinical guidelines. 2018. М.; 2018. 98 с. (In Russ.) Available at: https://spulmo.ru/obrazovatelnye-resursy/federalnye-klinicheskie-rekomendatsii/.Cabre M., Bolivar I., Pera G., Pallares R., Pneumonia Study Collaborative Group. Factors influencing length of hospital stay in community-acquired pneumonia: a study in 27 community hospitals. Epidemiol Infect. 2004;132(5):821-829. https://doi.org/10.1017/s0950268804002651.Cabre M., Bolivar I., Pera G., Pallares R., Pneumonia Study Collaborative Group. Factors influencing length of hospital stay in community-acquired pneumonia: a study in 27 community hospitals. Epidemiol Infect. 2004;132(5):821-829. https://doi.org/10.1017/s0950268804002651.Suter-Widmer I., Christ-Crain M., Zimmerli W., Albrich W., Mueller B., Schuetz Ph. Predictors for length of hospital stay in patients with community-acquired pneumonia: results from a Swiss multicenter study. BMC Pulm Med. 2012;12:21. https://doi.org/10.1186/1471-2466-12-21.Suter-Widmer I., Christ-Crain M., Zimmerli W., Albrich W., Mueller B., Schuetz Ph. Predictors for length of hospital stay in patients with community-acquired pneumonia: results from a Swiss multicenter study. BMC Pulm Med. 2012;12:21. https://doi.org/10.1186/1471-2466-12-21.Kozma C.M., Dickson M., Raut M.K., Mody S., Fisher A.C., Schein J.R., Mackowiak J.I. Economic benefit of a 1-day reduction in hospital stay for community-acquired pneumonia (CAP).J Med Econ. 2010;13(4):719-727. https://doi.org/10.3111/13696998.2010.536350.Kozma C.M., Dickson M., Raut M.K., Mody S., Fisher A.C., Schein J.R., Mackowiak J.I. Economic benefit of a 1-day reduction in hospital stay for community-acquired pneumonia (CAP). J Med Econ. 2010;13(4):719-727. https://doi.org/10.3111/13696998.2010.536350.Tellioglu E., Balci G., Mertoglu A. Duration of Stay of Patients with Community-Acquired Pneumonia in Influenza Season. Turk Thorac J. 2018;19(4):182-186. https://doi.org/10.5152/TurkThoracJ.2018.17108.Tellioglu E., Balci G., Mertoglu A. Duration of Stay of Patients with Community-Acquired Pneumonia in Influenza Season. Turk Thorac J. 2018;19(4):182-186. https://doi.org/10.5152/TurkThoracJ.2018.17108.Ostermann H., Garau J., Medina J., Pascual E., McBride K., Blasi F., REACH study group. Resource use by patients hospitalized with community-acquired pneumonia in Europe: analysis of the REACH study. BMC Pulm Med. 2014;14:36. https://doi.org/10.1186/1471-2466-14-36.Ostermann H., Garau J., Medina J., Pascual E., McBride K., Blasi F., REACH study group. Resource use by patients hospitalized with community-acquired pneumonia in Europe: analysis of the REACH study. BMC Pulm Med. 2014;14:36. https://doi.org/10.1186/1471-2466-14-36.Walden A.P., Clarke G.M., McKechnie S., Hutton P., Gordon A.C., Rello J. et al. Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort. Crit Care. 2014;18(2):R58. https://doi.org/10.1186/cc13812.Walden A.P., Clarke G.M., McKechnie S., Hutton P., Gordon A.C., Rello J. et al. Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort. Crit Care. 2014;18(2):R58. https://doi.org/10.1186/cc13812.Angus D.C., Marrie T.J., Obrosky D.S., Clermont G., Dremsizov T.T., Coley C. et al. Severe community-acquired pneumonia: use of intensive care services and evaluation of American and British Thoracic Society Diagnostic criteria. Am J Respir Crit Care Med. 2002;166(5):717-723. https://doi.org/10.1164/rccm.2102084.Angus D.C., Marrie T.J., Obrosky D.S., Clermont G., Dremsizov T.T., Coley C. et al. Severe community-acquired pneumonia: use of intensive care services and evaluation of American and British Thoracic Society Diagnostic criteria. Am J Respir Crit Care Med. 2002;166(5):717-723. https://doi.org/10.1164/rccm.2102084.Mbata G., Chukwuka C., Onyedum C., Onwubere B., Aguwa E. The role of complications of community acquired pneumonia on the outcome of the illness: a prospective observational study in a tertiary institution in eastern Nigeria. Ann Med Health Sci Res. 2013;3(3):365-369. Available at: https://pubmed.ncbi.nlm.nih.gov/24116315/.Mbata G., Chukwuka C., Onyedum C., Onwubere B., Aguwa E. The role of complications of community acquired pneumonia on the outcome of the illness: a prospective observational study in a tertiary institution in eastern Nigeria. Ann Med Health Sci Res. 2013;3(3):365-369. Available at: https://pubmed.ncbi.nlm.nih.gov/24116315/.Kolditz M., Ewig S. Community-Acquired Pneumonia in Adults. Dtsch Arztebl Int. 2017;114(49):838-848. https://doi.org/10.3238/arztebl.2017.0838.Kolditz M., Ewig S. Community-Acquired Pneumonia in Adults. Dtsch Arztebl Int. 2017;114(49):838-848. https://doi.org/10.3238/arztebl.2017.0838.Jain S., Self W.H., Wunderink R.G., Fakhran S., Balk R., Bramley A.M. et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015;373(5):415-427. https://doi.org/10.1056/NEJMoa1500245.Jain S., Self W.H., Wunderink R.G., Fakhran S., Balk R., Bramley A.M. et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015;373(5):415-427. https://doi.org/10.1056/NEJMoa1500245.Kolditz M.,Tesch F., Mocke L., Hoffken G., Ewig S., Schmitt J. Burden and risk factors of ambulatory or hospitalized CAP: A population based cohort study. Respir Med. 2016;121:32-38. https://doi.org/10.1016/j.rmed.2016.10.015.Kolditz M., Tesch F., Mocke L., Hoffken G., Ewig S., Schmitt J. Burden and risk factors of ambulatory or hospitalized CAP: A population based cohort study. Respir Med. 2016;121:32-38. https://doi.org/10.1016/j.rmed.2016.10.015.Maskin B., Fontan P.A., Spinedi E.G., Gammella D., Badolati A. Evaluation of endotoxin release and cytokine production induced by antibiotics in patients with Gram-negative nosocomial pneumonia. Crit Care Med. 2002;30(2):349-354. https://doi.org/10.1097/00003246-200202000-00014.Maskin B., Fontan P.A., Spinedi E.G., Gammella D., Badolati A. Evaluation of endotoxin release and cytokine production induced by antibiotics in patients with Gram-negative nosocomial pneumonia. Crit Care Med. 2002;30(2):349-354. https://doi.org/10.1097/00003246-200202000-00014.Hurley J.C. Towards clinical applications of anti-endotoxin antibodies; a reappraisal of the disconnect. Toxins (Basel). 2013;5(12):2589-2620. https://doi.org/10.3390/toxins5122589.Hurley J.C. Towards clinical applications of anti-endotoxin antibodies; a reappraisal of the disconnect. Toxins (Basel). 2013;5(12):2589-2620. https://doi.org/10.3390/toxins5122589.Bosshart H., Heinzelmann M. Targeting bacterial endotoxin: two sides of a coin. Ann N Y Acad Sci. 2007;1096:1-17. https://doi.org/10.1196/annals.1397.064.Bosshart H., Heinzelmann M. Targeting bacterial endotoxin: two sides of a coin. Ann N Y Acad Sci. 2007;1096:1-17. https://doi.org/10.1196/annals.1397.064.Kritselis I., Tzanetakou V., Adamis G., Anthopoulos G., Antoniadou E., Bristianou M. et al. The level of endotoxemia in sepsis varies in relation to the underlying infection: Impact on final outcome. Immunol Lett. 2013;152(2):167-172. https://doi.org/10.1016/j.imlet.2013.05.013.Kritselis I., Tzanetakou V., Adamis G., Anthopoulos G., Antoniadou E., Bristianou M. et al. The level of endotoxemia in sepsis varies in relation to the underlying infection: Impact on final outcome. Immunol Lett. 2013;152(2):167-172. https://doi.org/10.1016/j.imlet.2013.05.013.Мавзютова Г.А., Мухамадиева Л.Р., Фазлыева Р.М., Мирсаева Г.Х., Тюрина Е.Б. Рациональная иммунокоррекция в комплексной терапии внебольничной пневмонии. Медицинский совет. 2015;(16):68-73. https://doi.org/10.21518/2079-701X-2015-16-68-73.Mavzyutova G.A., Mukhamadieva L.R., Fazlyeva R.M., Mirsaeva G.Kh., Tyurina E.B. Rational immunotherapy in the combination treatment of community-acquired pneumonia. Meditsinskiy sovet = Medical Council. 2015;(16):68-73. (In Russ.) https://doi.org/10.21518/2079-701X-2015-16-68-73.Мухамадиева Л.Р, Мавзютова ГА., Фазлыева Р.М., Бикметова Н.Р Клиникоиммунологическая эффективность имунофана и полиоксидония в комплексной терапии внебольничной пневмонии. Медицинская иммунология. 2009;11(1):57-62. https://doi.org/10.15789/1563-0625-2009-1-57-62.Mukhamadieva L.R., Mavzyutova G.A., Fazlyeva R.M., Bikhmetova N.R. Clinical and immunological efficiency of immunofan and polyoxidonium in combined therapy of community-acquired pneumonia. Meditsinskaya immunologiya = Medical Immunology (Russia). 2009;11(1):57-62. (In Russ.) https://doi.org/10.15789/1563-0625-2009-1-57-62.

The authors declare that there are no conflicts of interest present.